The invention concerns novel methylenebisphosphonic acid derivatives, in particular novel halogen substituted methylenebisphosphonic ester acids and ester salts, as well as processes for the preparation of these novel compounds and pharmaceutical compositions comprising such novel compounds.
Several publications disclose methylenebisphosphonic acids, their salts or some tetraesters, but there are only a few disclosures of corresponding halogen substituted tri-, di- and monoesters (partial esters). The U.S. Pat. No. 4,478,763 (1984) discloses a new process for the preparation of unsymmetrical isopropyl esters of (mono- and difluoromethylene)bisphosphonic acids. As further publications disclosing fluorine substituted compounds, the following may be mentioned: J. Org. Chem., 51, (1986), 4788, J. Am. Chem. Soc., (1987) 5542, and Bioorg. Chem., (1988) 111. Thus neither the properties of the novel partial esters of (halogenmethylene)bisphosphonic acids and their salts according to the invention, nor their use as medicaments, have been investigated.